Kingdom of Sixteen Kingdoms Period), Khitans (founders of Liao Dynasty), and Jurchens (founders of Jin Dynasty). Those Altaic migrants may have included very few or no individuals carrying the ALDH2*504Lys allele because present Altaic populations have a low frequency of the allele. The merging of these Altaic populations could have decreased the proportion of ALDH2*504Lys in the Central Chinese populations. On the other hand, some as yet unknown protective effects of ALDH2*504Lys against diseases might also have contributed to the increased frequency of this allele in Southern Chinese. Since migrations to South China resulted from wars, the refugees may have been subjected to considerable stress and a selective advantage could have had great impact. We can speculate that the ALDH2*504Lys heterozygotes had an advantage because they tended to drink less alcohol or had some other advantage (Chen et al., 1999). The recent appreciation of other metabolic/pharmacologic roles for ALDH2 (Li et al., 2006; Larson et al., 2007; Chen et al., 2008) suggest that if selective factors are responsible for the high ALDH2*2 frequency in East Asia, their nature may be unrelated to the current association with esophageal cancer or ethanol metabolism. Alternative hypotheses of increased resistance to some disease organisms
